ALDH Activity Indicates Increased Tumorigenic Cells, But Not Cancer Stem Cells, in Prostate Cancer Cell Lines

Background: Cancer stem cells (CSCs) have been shown to be a small stem cell-like cell population which appears to drive tumorigenesis, tumor recurrence and metastasis. Thus, identification and characterization of CSCs may be critical to defining effective anticancer therapies. In prostate cancer (PCa), the CD44 + cell population appears to have stem cell-like properties including being tumorigenic. The enzyme aldehyde dehydrogenase (ALDH) has been found to identify hematopoietic stem cells and our aim was to determine the utility of ALDH activity and CD44 in identifying PCa stem cell-like cells in PCa cell lines. Materials and Methods: LNCaP cells and PC-3 cells were sorted based on their expression of CD44 and ALDH activity. The cell populations were investigated using colony-forming assays, invasion assays, sphere formation experiments in a non-adherent environment and 3-D Matrigel matrix culture to observe the in vitro stem-cell like properties. Different sorted cell populations were injected subcutaneously into NOD/SCID mice to determine the corresponding tumorigenic capacities. Results: ALDH hi CD44 + cells exhibit a higher proliferative, clonogenic and metastatic capacity in vitro and demonstrate higher tumorigencity capacity in vivo than did ALDH lo CD44 - cells. The tumors recapitulated the population of the original cell line. However, ALDHlo CD44 - cells were able to develop tumors, albeit with longer latency periods. Conclusion: ALDH activity and CD44 do not appear to identify PCa stem cells; however, they do indicate increased tumorigenic and metastatic potential, indicating their potential importance for further exploration. Prostate cancer (PCa) is the third leading cause of cancer- related deaths among men in America (1). In 2006, an estimated 27,000 American men died of prostate cancer and an estimated 230,000 new cases were diagnosed (1). The concept of the 'cancer stem cell' (CSCs) was introduced more than 50 years ago when it was recognized that only a small proportion of cells (0.01%-1%) in tumor isolates are clonogenic and extensively proliferative in vitro and in vivo (2, 3), indicating that these cells might represent tumor stem cells. The CSC hypothesis was recently revived following the development of novel methods for identification, purification and characterization of normal stem cells. The most stringent